Open AccessRHBDD1 promotes proliferation, migration, invasion and EMT in renal cell carcinoma via the EGFR/AKT signaling pathway
Author(s) -
Mingyang Li,
Licheng Cai,
Xingyuan Wang,
Yipeng Yu,
Wengang Jian,
Guochang Bao,
Zhiming Gao,
Junsheng Guo,
Jian Zhang,
Chunsheng Li,
Cheng Zhang
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12466
Subject(s) - epithelial–mesenchymal transition , protein kinase b , vimentin , cancer research , pi3k/akt/mtor pathway , cell growth , cell migration , biology , cell cycle , oncogene , gene knockdown , signal transduction , blot , cell , cancer , cell culture , microbiology and biotechnology , metastasis , immunology , immunohistochemistry , biochemistry , genetics , gene
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with a poor prognosis and high mortality rate. The increasing incidence of RCC poses a serious threat to human health. It is well‑documented that rhomboid domain‑containing protein 1 (RHBDD1) plays a vital role in cancer progression. The present study was designed to identify the biological functions of RHBDD1 in RCC and investigate the underlying regulatory mechanism, aiming to explore the novel molecular therapeutic targets for RCC. The protein and mRNA expression levels of RHBDD1 in normal renal tubule epithelium and human RCC cell lines were analyzed using western blotting and reverse transcription‑quantitative PCR. Cell proliferation was determined using Cell Counting Kit‑8 assays. Wound healing and Transwell assays were performed to determine cell migration and invasion, respectively. In addition, key proteins related to migration, invasion and epithelial‑mesenchymal transition (EMT), such as matrix metalloproteinase (MMP)2, MMP9, MMP13, E‑cadherin, N‑cadherin, vimentin and Slug, were analyzed using western blotting. In addition, the EGFR/AKT signaling pathway was further studied using western blotting to determine the potential molecular mechanism. The results of the present study revealed that RHBDD1 expression levels were significantly upregulated in RCC cell lines. The knockdown of RHBDD1 inhibited cell proliferation, migration, invasion and EMT, while the overexpression of RHBDD1 promoted cell proliferation, migration, invasion and EMT in RCC. In addition, the knockdown of RHBDD1 suppressed the activation of the EGFR/AKT signaling pathway, while the overexpression of RHBDD1 activated the EGFR/AKT signaling pathway. Moreover, these stimulatory effects of RHBDD1 overexpression on RCC progression and the EGFR/AKT signaling pathway were partly reversed by gefitinib, an EGFR inhibitor. In conclusion, the findings of the present study suggested that RHBDD1 may be a crucial regulator of RCC by modulating the EGFR/AKT signaling pathway. The present study may provide a theoretical basis and potential targets for RCC treatment.